Computational identification of small molecules for increased gene expression by synthetic circuits in mammalian cells.

ABSTRACT: Engineering mammalian cells with synthetic circuits drives innovation in next-generation biotherapeutics and industrial biotechnology. However, applications often depend on cellular productivity, which is constrained by finite cellular resources. Here, we harness computational biology to identify drugs that boost productivity without additional genetic modifications. We perform RNA-sequencing on cells expressing an incoherent feed-forward loop (iFFL), a genetic circuit that enhances operational capacity. To find drugs that mimic this effect, we use DECCODE (Drug Enhanced Cell COnversion using Differential Expression), an unbiased method that matches our transcriptional data with thousands of drug-induced profiles. Among the compound candidates, we select Filgotinib, that enhances expressio

SUBMITTER: Pisani M 

PROVIDER: S-EPMC12322086 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature